Gene Therapy for -Associated Retinal Diseases Helps to Delay Retinal Degeneration and Vision Loss.

Purpose: The aim of study was to establish -associated inherited retinal disease (-IRD) mouse model and to identify the best timepoint for gene therapy.

Methods: We induced retinal degeneration in mice using a bright light. We clarified the establishment of -IRD mouse model by analyzing the thickness of retinal layers and electroretinography (ERG). -IRD mice received a subretinal injection of adeno-associated virus 2/8-packaged cDNA for treatment. We evaluated the visual function and retinal structure in the treated and untreated eyes to identify the best timepoint for gene therapy.

Results: -IRD mice showed significant differences in ERG amplitudes and photoreceptor survival compared to mice. Preventive gene therapy not only maintained normal visual function but also prevented photoreceptor loss. Salvage gene therapy could not reverse the retinal degeneration phenotype of -IRD mice, but it could slow down the loss of visual function.

Conclusion: The light-induced retinal degeneration in our mice indicated that a defect in alone was sufficient to cause visual dysfunction and photoreceptor degeneration, which reproduced the phenotypes observed in -IRD patients. This model is suitable for gene therapy studies. Early treatment of the primary defect helps to delay the later onset of photoreceptor degeneration and maintains visual function in -IRD mice.